Document Detail


Positive immunohistochemical staining of KIT in solid-pseudopapillary neoplasms of the pancreas is not associated with KIT/PDGFRA mutations.
MedLine Citation:
PMID:  16778826     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Solid-pseudopapillary neoplasms of the pancreas are uncommon neoplasms of low malignant potential and of uncertain histogenesis. A small percentage of patients develop metastatic disease and some succumb to disease. The management of patients with metastatic disease or unresectable tumor, and patients who are just not good surgical candidates is problematic. Novel therapy targets are needed. Successful treatment of metastatic and unresectable gastrointestinal stromal tumors with KIT kinase inhibitor, imatinib mesylate (Gleevec), makes it intriguing to look at the status of KIT in solid-pseudopapillary neoplasms of the pancreas. In this study, we investigated KIT expression in 50 solid-pseudopapillary neoplasms by immunohistochemical staining. Of the 50 (50%) solid-pseudopapillary neoplasms, 25 showed diffuse expression (in >50% neoplastic cells) of KIT and additional five (10%) cases showed focal staining (in 10-50% neoplastic cells). Expression of KIT was not associated with tumor behavior and prognosis. A subset of 11 cases showing diffuse KIT expression detected by immunohistochemical staining were further evaluated for the presence of activating mutations in KIT exons 9, 11, 13 and 17, and PDGFRA exons 12 and 18 using PCR amplification followed by direct sequencing. However, no KIT or PDGFRA mutations were identified in any of these 11 cases tested, suggesting that the overexpression of KIT is probably not due to activating mutations in KIT or PDGFRA. The exact mechanism of KIT overexpression in solid-pseudopapillary neoplasms remains to be elucidated. One possible mechanism is gene dose effect (increased copies of KIT gene). Experience in gastrointestinal stromal tumors and other tumors have shown that mutation-mediated activation of KIT or PDGFRA is a prerequisite for clinical response with imatinib mesylate. Thus, lack of mutations in KIT or PDGFRA in solid-pseudopapillary neoplasms suggests that imatinib mesylate is less likely to be effective in the treatment for patients with metastatic disease or unresectable tumor, and patients who are just not good surgical candidates.
Authors:
Dengfeng Cao; Cristina Antonescu; Grace Wong; Jordan Winter; Anirban Maitra; N Volkan Adsay; David S Klimstra; Ralph H Hruban
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Publication Detail:
Type:  Journal Article     Date:  2006-06-16
Journal Detail:
Title:  Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc     Volume:  19     ISSN:  0893-3952     ISO Abbreviation:  Mod. Pathol.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-23     Completed Date:  2006-10-31     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8806605     Medline TA:  Mod Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1157-63     Citation Subset:  IM    
Copyright Information:
Published online 16 June 2006.
Affiliation:
Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. dcao1@jhmi.edu
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Carcinoma, Papillary / genetics,  metabolism*,  mortality
Cell Count
Child
DNA Mutational Analysis
Female
Humans
Immunohistochemistry / methods
Male
Middle Aged
Mutation*
Pancreatic Neoplasms / genetics,  metabolism*,  mortality
Proto-Oncogene Proteins c-kit / genetics,  metabolism*
Receptor, Platelet-Derived Growth Factor alpha / genetics,  metabolism*
Survival Rate
Tumor Markers, Biological / metabolism
Chemical
Reg. No./Substance:
0/Tumor Markers, Biological; EC 2.7.10.1/Proto-Oncogene Proteins c-kit; EC 2.7.10.1/Receptor, Platelet-Derived Growth Factor alpha

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